Evidence of novel Treponema phylotypes implicated in contagious ovine digital dermatitis and association of treponemes with major lameness causing foot pathogens.

In this study 269 swabs collected from 254 ovine foot lesions and 15 apparently healthy ovine feet were screened by PCR for the presence of major lameness causing foot pathogens viz. Treponema species, D. nodosus, F. necrophorum and T. pyogenes with the presumption that ovine foot lesion positive for Treponema species alone or in association with other three pathogens were categorized as contagious ovine digital dermatitis (CODD). While samples positive for D. nodosus alone or its combination with F. necrophorum and T. pyogenes were considered as footrot (FR) and samples in which F. necrophorum or T. pyogenes was found either alone or in combination were considered as interdigital dermatitis (ID). The overall occurrence of Treponema sp. in ovine foot lesions was 48.0%, and ranged from 33 to 58%. In Treponema positive samples D. nodosus, F. necrophorum and T. pyogenes were present in 34 (27.4%), 66 (54.4%) and 84 (68.5%) in contrast to Treponema negative samples in which these were present in 15 (11.1%), 20 (14.12%) and 17 (12.6%) samples, respectively. The data signifies that Treponema sp. are significantly associated with these foot pathogens and their different combinations with Treponema sp. influence the severity of CODD lesion. The identification of Treponema phylotypes was done by sequencing the 16S rRNA gene fragment of ten representative samples. Out of ten sequences, four (Trep-2, Trep-4, Trep-7 and Trep-10) were identical to Treponema sp. phylotype 1 (PT1) that belongs to phylogroup T. refringens-like, one sequence (Trep-1) was genetically close (90% sequence homology) to Treponema brennaborense while five sequences (Trep-3, Trep-5, Trep-6, Trep-8 and Trep-9) matched with uncultured bacterium clones of treponemes forming separate monophyletic group in phylogenetic tree and could represent new digital dermatitis phylogroup presently containing five ovine specific phylotypes. This is the first report on the presence of Treponema phylotypes other than three digital dermatitis (DD) Treponema phylogroups viz. T. phagedenis-like, T. medium/T. vincentii-like, and T. pedis-like that are frequently detected in CODD lesions. Metagenomic analysis of two representative samples revealed the abundance of genus Treponema in CODD lesion while this genus was absent in swab collected from clinically healthy foot suggesting that it might play primary role in producing CODD. These findings may further aid in understanding the etiopathogenesis of CODD and could help to develop appropriate treatment and mitigation strategies to combat the disease.

Delineating binding potential, stability of Sulforaphane-N-acetyl-cysteine in the active site of histone deacetylase 2 and testing its cytotoxicity against distinct cancer lines through stringent molecular dynamics, DFT and cell-based assays.

Histone deacetylase 2 (HDAC2), an isozyme of Class I HDACs has potent imputations in actuating neurodegenerative signaling. Currently, there are sizeable therapeutic disquiets with the use of synthetic histone deacetylase inhibitors in disease management. This strongly suggests the unfulfilled medical necessity of plant substitutes for therapeutic intervention. Sulforaphane-N-acetyl-cysteine (SFN-N-acetylcysteine or SFN-NAC), a sulforaphane metabolite has shown significantly worthier activity against HDACs under in vitro conditions. However, the atomistic studies of SFN-NAC against HDAC2 are currently lacking. Thus, the present study employed a hybrid strategy including extra-precision (XP) grid-based flexible molecular docking, molecular mechanics generalized born surface area (MM-GBSA), e-Pharmacophores method, and molecular dynamics simulation for exploring the binding strengh, mode of interaction, e-Pharmacophoric features, and stability of SFN-NAC towards HDAC2. Further, the globally acknowledged density functional theory (DFT) study was performed on SFN-NAC and entinostat individually in complex state with HDAC2. Apart from this, these inhibitors were tested against three distinct cancer cell models and one transformed cell line for cytotoxic activity. Moreover, double mutant of HDAC2 was generated and the binding orientation and interaction of SFN-NAC was scrutinized in this state. On the whole, this study unbosomed and explained the comparatively higher binding affinity of entinostat for HDAC2 and its wide spectrum cytotoxicity than SFN-NAC.

Postpartum Acute Kidney Injury: Experience of a Tertiary Care Center.

Pregnancy-related-acute kidney injury (PR-AKI) had decreased from 40% to 20% in 1960 to <10% in recent series, mostly due to meticulous antenatal management. Postpartum-AKI (PP-AKI) resulting from late obstetric complications has become more apparent after improvement in antenatal care and legalization of medical termination of pregnancy. Women with renal injury in peripartum period admitted to our hospital over a period of 2 years (April 2013 to May 2015) were studied. Of 713 patients of AKI admitted, 61 had PR-AKI with an incidence of 4.27%. Out of the 61 patients, 28 had PP-AKI with an incidence of 1.96%. The mean age of patients with PP-AKI was 26.10 ± 4.3 years. Sepsis was the most common cause accounting for 11 (39.28%) cases followed by postpartum hemorrhage (PPH) in 7 (25%) cases. Renal biopsy was done in nine patients, out of whom four were having cortical necrosis. Patients having diffuse cortical necrosis remained dialysis-dependent. High contribution of sepsis and PPH to PP-AKI in our setting makes it an ideal target for rectification. Protocolized peripartum monitoring and standard clinical practices of asepsis will go long way in decreasing the incidence of PP-AKI and maternal morbidity in our valley.

Targeting leukemic side population cells by isatin derivatives of nicotinic acid amide.

Side population (SP) cells mediate chemoresistance in leukemia. However, chemical inhibition approach to target SP cells has been poorly studied. Herein, we report the discovery of isatin derivatives of nicotinic acid amide as potent side population cell inhibitors. The selected derivatives showed superior potency over the reference drug verapamil. Furthermore, the treatment increased chemosensitivity and inhibited the cell proliferation on three different leukemic cell lines, K562, THP-1 and U937, suggesting that both SP and the bulk of leukemic cells are affected. Moreover, treatment with the most potent compound Nic9 reduced the expression of ABCG2, demonstrating that side population inhibition effect of the target derivatives is at least via ABCG2 inhibition. Importantly, the target derivatives induced erythrocyte/dendritic differentiation to leukemic cells mainly through Musashi/Numb pathway modulation.

Role of preoperative chemotherapy in squamous cell carcinoma of esophagus in kashmir, a cancer belt - a pilot study.

BACKGROUND: Esophageal carcinoma is the fifth leading gastrointestinal malignancy and is one of the leading causes of cancer related death. Despite improvements in surgical technique over the last few decades, the outcome has been dismal, with overall 5 year survival not exceeding 15%-25%. AIMS AND OBJECTIVES: To evaluate the effect of preoperative chemotherapy on resectability, complication rate and overall survival in patients with squamous cell carcinoma esophagus. MATERIALS AND METHODS: 50 patients with histologically confirmed squamous cell carcinoma (SCC), with localised or loco-regional disease (stage 4 excluded) were divided into 2 groups. Group A patients were subjected to 2-3 cycles of pre-operative chemotherapy (5FU-CDDP), whereas Group B patients were directly operated on. OBSERVATIONS: 3 (12%) patients in group A showed complete pathological response to chemotherapy and 18 (72%) showed a partial response, with four patients (16%) showing resistance to chemotherapy. There was no statistically significant difference in terms of response to chemotherapy with respect to degree of differentiation of tumor. There was no significant difference in the overall resectability rates between the two groups (p > 0.05), but R0 resection was achieved in 20 (80%) of group A and only 10 (40%) of group B, the difference being statistically significant (p < 0.05). The rate of overall complications was also much higher in the control group. Initially there was no significant difference in the survival between the two groups, but later (20 months) the study group showed a slight non-significant advantage. CONCLUSION: Preoperative chemotherapy significantly increases the rate of R0 resection without significantly increasing postoperative morbidity and mortality in patients with squamous cell carcinoma of esophagus. However, to assess the impact on survival the study period needs to be extended.

Management of biliary ascariasis in children living in an endemic area.

BACKGROUND: One quarter of the world's population is known to be infected with ascariasis. It is endemic in various parts of the Indian subcontinent with a high incidence in the Kashmir valley. Although intestinal obstruction is the commonest complication of ascariasis in children, biliary ascariasis remains the second most common complication. We aimed to study the various types of clinical presentations, complications and different diagnostic tools and to assess various options for the management of biliary ascariasis. MATERIALS AND METHODS: Sixty-one cases of ultrasound documented hepatobiliary ascariasis were studied prospectively over a period of 3 years from Jan 2003 to Dec 2005 at the Sheri-Kashmir Institute of Medical Sciences in Srinagar, Kashmir. All patients were children aged between 3 and 14 years. All patients were admitted to hospital and put on intravenous fluids, nothing per os until patients were symptom-free, broadspectrum antibiotics and antispasmodics. All patients received antihelminthics in the form of albendazole 400 mg as soon as patients could accept oral medication. Conservative management was continued until the patients were symptom-free. Endoscopic extraction was deferred until 3 weeks later except in patients with pyogenic cholangitis where urgent endoscopic intervention was carried out. Surgical intervention was carried out if both conservative management and endoscopic extraction failed or ERCP could not be performed for technical reasons or complications developed. RESULTS: The most common presentation was upper abdominal pain in 36 (59%) patients followed by vomiting of worms in 20 (33.3%) cases. Complications included cholangitis in 8 (13.1%), obstructive jaundice in 7 (11.4%), acute pancreatitis in 1 (1.6%) and hepatic abscess in 1 (1.6%) patient. Spontaneous passage of worms from the biliary ducts was observed in 44 (72.1%) patients. ERCP was successful in 8 (13.1%) patients, and 9 (14.7%) patients needed surgical intervention. CONCLUSION: In endemic countries, ascariasis should be suspected in patients with biliary disease. Most patients respond to conservative management although a few may need surgical intervention. Although this disease is prevalent in developing countries, because of increased travel and migration, clinicians elsewhere should be aware of the problems associated with ascariasis.

Molecular epidemiology of ovine herpesvirus type 2 infection in Kashmir, India.

The aims of this investigation were to determine the prevalence of ovine herpesvirus type 2 (OvHV-2) (the causative agent of malignant catarrhal fever) infection in cattle, the carrier status of sheep and goats, and to define the pattern of acquisition of OvHV-2 in lambs under natural flock conditions in Kashmir, India. None of the buffy coat samples from 21 lambs contained OvHV-2 DNA sequences up to 28 days after birth, only one lamb had sequences of OvHV-2 DNA as early as 29 days after birth, and they were detected in the other 20 lambs when they were between 43 and 94 days of age. Sequences of OvHV-2 DNA were detected in buffy coat samples from 28 (85 per cent) of 33 adult sheep and in 16 (61 per cent) of 26 samples from adult goats by hemi-nested PCR. Seventeen (31 per cent) of 55 cattle with malignant catarrhal fever-like clinical signs had sequences of OvHV-2 DNA in their blood, and nine of the 17 died, all of them during the months of April to November, between November 2002 and March 2004. No clinical cases of sheep-associated malignant catarrhal fever was recorded during the months of December to March. The overall prevalence of OvHV-2 infection in the cattle in the region was estimated to be less than 1 per cent.

Minimally invasive transthoracotomy-transphrenotomy for concurrent hepatic and pulmonary hydatid disease.

BACKGROUND: Combined liver and lung hydatid cysts are rare, but pose a challenge in terms of accessibility. The objective of the study was to find an alternative approach to conventional two-stage posterolateral thoracotomy and laparotomy or single-stage extensive thoracolaparotomy. METHODS: Twenty-five patients with right lung and liver hydatid disease underwent single-stage anterior minithoracotomy and phrenotomy. Primary diagnostic tools were chest radiography, ultrasonography and serology. The preferred mode of management of hydatid cysts was enucleation and partial or total capitonnage. RESULTS: Thirty-six (13.5 per cent) of 267 patients had concurrent hepatic and pulmonary hydatid cysts. Among the 25 patients who had anterior minithoracotomy and phrenotomy the male : female ratio was 2 : 1. Mean operating time was 75 min. Morbidity was negligible and postoperative recovery was prompt. All of the patients survived. The mean hospital stay was 5.2 days. Overall observations were encouraging. CONCLUSION: This minimally invasive approach is associated with less morbidity and better cosmesis than conventional procedures. It represents an excellent alternative to other procedures in selected patients.

Fate of hypertension after repair of coarctation of the aorta in adults.

BACKGROUND: Unrepaired aortic coarctation is known to have a detrimental effect on survival. The benefit of coarctation repair on systolic hypertension in adults has been questioned. This retrospective study was conducted to evaluate the impact of repair of aortic coarctation on systolic hypertension in adults. METHODS: Repair of aortic coarctation was performed in 84 patients aged 16-54 (mean 29) years. All patients were hypertensive before surgical intervention (mean systolic blood pressure 162 mmHg; mean diastolic blood pressure 93 mmHg). All patients underwent echocardiography and/or cardiac catheterization. The peak mean systolic gradient across the coarctation was 60 mmHg. The patients were followed after coarctation repair for between 1 and 12 (mean 5.2) years. RESULTS: There was significant regression of hypertension (P < 0.001) in all patients. Thirty-five patients (42 per cent) did not need any antihypertensive medication 3 months after surgery. The prevalence of hypertension at the last follow-up (after mean 5.2 years) was 31 per cent. CONCLUSION: Surgical repair of coarctation of the aorta in adults leads to regression of systolic hypertension and a decreased requirement for antihypertensive medication.

Discs Lost, a novel multi-PDZ domain protein, establishes and maintains epithelial polarity.

Polarization of epithelial cells depends on a hierarchical process whereby specific membrane-associated proteins become targeted to specialized membrane domains. Here, we describe a novel Drosophila protein, Discs Lost (DLT), that plays a crucial role in the polarization of embryonic epithelia during cellular blastoderm formation. At subsequent stages of development, DLT interacts with the apical determinant Crumbs (CRB) and the laterally localized protein Neurexin IV (NRX IV). Mutations in dlt or double-stranded RNA interference lead to aberrant localization of CRB and NRX IV and cause a concomitant loss of epithelial cell polarity. Hence, DLT is required to establish and maintain cell polarity and participates in different molecular complexes that define apical and lateral membrane domains.

Purification of 3,5-dichlorocatechol 1,2-dioxygenase, a nonheme iron dioxygenase and a key enzyme in the biodegradation of a herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), from Pseudomonas cepacia CSV90.

An enzyme which cleaves the benzene ring of 3,5-dichlorocatechol has been purified to homogeneity from Pseudomonas cepacia CSV90, grown with 2,4-dichlorophenoxyacetic acid (2,4-D) as the sole carbon source. The enzyme was a nonheme ferric dioxygenase and catalyzed the intradiol cleavage of all the examined catechol derivatives, 3,5-dichlorocatechol having the highest specificity constant of 7.3 microM-1s-1 in an air-saturated buffer. No extradiol-cleaving activity was observed. Thus, the enzyme was designated as 3,5-dichlorocatechol 1,2-dioxygenase. The molecular weight of the native enzyme was ascertained to be 56,000 by light scattering method, while the M(r) value of the enzyme denatured with 6 M guanidine-HCl or sodium dodecyl sulfate was 29,000 or 31,600, respectively, suggesting that the enzyme was a homodimer. The iron content was estimated to be 0.89 mol per mole of enzyme. The enzyme was deep red and exhibited a broad absorption spectrum with a maximum at around 425 nm, which was bleached by sodium dithionite, and shifted to 515 nm upon anaerobic 3,5-dichlorocatechol binding. The catalytic constant and the Km values for 3,5-dichlorocatechol and oxygen were 34.7 s-1 and 4.4 and 652 microM, respectively, at pH 8 and 25 degrees C. Some heavy metal ions, chelating agents and sulfhydryl reagents inhibited the activity. The NH2-terminal sequence was determined up to 44 amino acid residues and compared with those of the other catechol dioxygenases previously reported.

A double-blind randomized cross-over comparison of high-dose prochlorperazine with high-dose metoclopramide for cisplatin-induced emesis.

This double-blind randomized cross-over study was conducted to compare the safety and efficacy of high-dose prochlorperazine infusion and dexamethasone (HDPD) with an effective and safe combination of high-dose metoclopramide and dexamethasone (HDMD) in controlling cisplatin-induced emesis. None of the patients entering the study had received any prior chemotherapy. High-dose cisplatin was administered on an inpatient basis. Twenty eligible patients were analyzed based on the assessment made 24 h after the chemotherapy. The parameters compared were severity and duration of nausea and vomiting, severity of retching and side effects. Significantly less vomiting and retching episodes were recorded with HDPD combination. The severity of nausea was also less with this combination. There was no significant difference in the incidence of side effects.